Hemoglobinopathies

Question 1

What are the genotypes that will produce sickle cell disease?

Answer 1

Hb SS, Hb SC (sickle and crystallizing mutations) and Hb SB-thal

note sickle cell mutation effects B class
HbA thalasemias can be some what sheltering

Question 2

Are there any clinical symptoms for sickle cell trait?

Answer 2

(HbAS) usually has no serious clinical consequences, although serious clinical consequences can occur during intensive training

Question 3

Deoxygenation of sickle mutant Hb leads to what 3 main cellular changes.

Answer 3

increased K+ influx
increased cell density/dehydration
increased polymerization of Hb

conditions that cause rightward shift of hemoglobin binding curve tend to promote polymerization (decreased pH, increased 1,3 DPG), slowed transit time and endothelial adhesion

Question 4

Name as many clinical sequalae of sickle cell as possible. (16)

Answer 4

painful episodes
pneumococcal disease
acute chest syndrome
splenic infarction
splenic sequestration (acute enlargement entrapping RBC)
stroke
osteonecrosis
priapism
retinopathy
leg ulcers
gallstones
renal abnormalities
osteopenia
nutritional deficiencies
placental insufficiency
pulmonary HTN
dactylitis
(occlusive vasculopathy- moya-moya pattern)

Question 5

Contrast symptoms correlated with higher hemoglobin v. lower hemoglobin.

Answer 5

higher: painful epidsodes, acute chest syndrome, osteonecrosis, proliferative retinopathy
lower: stroke, priapism, leg ulcers

Question 6

What treatments are currently used for SC patients?

Answer 6

hydroxyurea (changes adhesion and hydration of RBC, promotes fetal hemoglobin etc.)
opiates and hydration for painful crises
pneumococcal vaccination, Abx prophylaxis
retinal surveillance
transfusions for serious manifestations

stem cell transplant

Question 7

In thalassemia, unbalanced global chain synthesis causes ________ (seen on smear), ineffective erythropoiesis and hemolysis.

Answer 7

microcytosis, a thal will have inclusion bodies of HbH (B tetramers- visible with supravital stain) and B thal will have precipitate of a tetramers

Question 8

What are Heinz bodies?

Answer 8

an inclusion body that contains denatured hemoglobin, can be result of G6-PD deficiency (classically leading to bite cells) as well as in thalassimias (ie. B4 = HbH)

Question 9

What are the symptomatic genotypes of a thalassemia ?

Answer 9

aa/a- and aa/– lead to mild microcytosis

a-/– leads to HbH disease
–/– leads to Hydrops fetalis and hemoglobin Bart’s

Question 10

Characterize the hemaglobin of a patients with Beta thalassemia major.

Answer 10

no beta chain is produced (no HbA - 2a, 2B)

Question 11

What are the pathologic consequences of Beta thalassemia major?

Answer 11

no HbA is produced

severe microcytic anemia occurs, marrow expands, iron overload (increased absorption and transfusions)

hemolysis, splenomegaly

growth failure and death

Question 12

What are the key features of thalassemia intermedia on smear?

Answer 12

microcytic anemia with target cells, nucleated RBC and other bizarre red cell forms

Question 13

What are the features of a thalassemia minor and HgbH ?

Answer 13

microcytosis, hypochromia, varying levels of anisocytosis, poikilocytosis, target cells (HgbH)

Question 14

Hemoglobin E is associated with which population?

Answer 14

(B mutation)

clinically significant mutation most common in patients of southeast asian decent

Question 15

A possible treatment for SC patients requiring frequent transfusions, a port may be placed for this type of transfusion.

Answer 15

erythrocytopheresis

Question 16

Acanthocytes are most commonly associated with which liver malfunction?

Answer 16

due to alteration of membrane lipids, associated with absence of apolipidproteins (severe liver disease)

Question 17

Which two cellular features are most characteristic of a patient without a spleen

Answer 17

Howell-Jolly Bodies (retained nuclear material)

Pappenheimer Bodies (ribosomal, lysosomal, mitochondrial and iron rich material) ** can indicate iron handling problems and hemoglobinopathies

Question 18

Large, chunky, squarish cells that are more polygonal in shape appear in response to crystallization of hemoglobin, what is the corresponding genotype?

Answer 18

Bc

Question 19

What are likely features of a smear from a SC patient besides sickle cells?

Answer 19

Howell-Jolly bodies if spleen has been infarcted
nucleated RBC due to reticulocytosis
and target cels

Question 20

Presence of target cells is significant for what underlying pathology?

Answer 20

inappropriate defective globin chain synthesis

Question 21

Discuss the RBC, MCV and RDW of a thalassemia, B thalassemia and Fe deficiency

Answer 21

a thal: high RBC, low MCV, low RDW (typically minimal anemia)
B thal: high RBC, low MCV, low RDW (basophilic stippiling is common)

Fe deficiency: low MCV, low RBC, high RDW

Question 22

In which conditions would you expect to find basophilic stippling?

Answer 22

disorder or defective hemoglobin synthesis (thalassemia and lead poisoning), can also be found in normal individuals

Question 23

Slightly elevated A2 should make you at least consider which hemoglobinopathy?

Answer 23

B thalasemmia depending on the degree of elevation either major or minor

Question 24

How would you expect iron studies to change in a patient with B thalassemia trait?

Answer 24

no change

Question 25

If given a HCT and red blood cell count?

Answer 25

calculate the MCV to see if the patient had microcytic or macrocytic cells [(HCT/ RC count)x10]